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PubMed1976

Effect of cyproheptadine and combinations of cyproheptadine and amphetamine on intermittently reinforced lever-pressing in rats.

Effects of the tryptamine antagonist, cyproheptadine, as well as of amphetamine, chlordiazepoxide, and combinations of cyproheptadine with amphetamine on lever-pressing behavior of rats were determined. A multiple, fixed-interval, 2 min fixed-ratio, 15 response schedule of water presentation was used. The three drugs affected fixed-interval fixed-ratio responding in a rate-dependent way, lower rates being more increased whereas higher rates were relatively more decreased. Cyproheptadine increased low response rates to a lesser extent than amphetamine, but increased high response rates that were little affected or only decreased by amphetamine. The combination of cyproheptadine and amphetamine increased response rates to a higher extent than either of the drugs alone. In addition, the rate-suppressant effects of the highest doses of amphetamine were also enhanced by cyproheptadine. These results show that cyproheptadine can increase nonpunished responding and suggest that cyproheptadine and amphetamine act synergistically, but through different mechanisms, upon multiple fixed-interval fixed-ratio performance.

Amphetamine↗
PubMed1984

Developmental changes in the activity and substrate specificities of mouse brain monoamine oxidase.

Developmental changes in monoamine oxidase (MAO) activity in the mouse brain were investigated with the substrates beta-phenylethylamine (PEA), tryptamine, and 5-hydroxytryptamine (5-HT). In the newborn brain, MAO activity towards PEA was found to be much lower than the adult and to be inhibited by clorgyline in a double-sigmoidal fashion. The inhibition curve shifted to a single-sigmoidal pattern with age. MAO activity towards 5-HT as substrate was inhibited by 90% and in a single-sigmoidal manner by clorgyline throughout the postnatal life. Lineweaver-Burk plots with PEA as substrate presented two linear lines (apparent Km: 28.6 and 4.1 microM) for the newborn and one line (apparent Km: 11.4 microM) for the adult, respectively. The plot with high Km value for the newborn brain disappeared in a clorgyline-treated preparation. These findings suggest that age-dependent alterations in the ratio of MAO-A/MAO-B activity affect the substrate specificity of the enzyme.

Animals↗
PubMed1986

Effects of p-chlorophenylalanine on cortical monoamines and on the activity of noradrenergic neurons.

The catecholamines noradrenaline, dopamine, adrenaline, the indoleamine 5-hydroxy-tryptamine (5-HT; serotonin), and some of their major metabolites were assayed, using high performance liquid chromatography (HPLC), in the neocortex of normal rats as well as in animals in which 5-HT synthesis had been inhibited with p-chlorophenylalanine. Besides important depletions in serotonin and in 5-hydroxyindole-3-acetic acid, noradrenaline levels were significantly reduced, but the content in 3-methoxy-4-hydroxyphenylglycol was increased, indicating an augmented utilization of this amine. The levels of dopamine and 3-methoxytyramine were also reduced, although homovanillic acid and 3,4-dihydroxyphenylacetic acid levels remained constant. The spontaneous unitary activity of identified noradrenergic neurons in the Locus coeruleus was increased, indicating an hyperactivity of this system. These results can be interpreted in relation to functional interactions between the catecholamines and serotonin; i.e.: a decrease in endogenous serotonin results in the loss of a negative feedback control of noradrenaline release.

Adrenergic Fibers↗
PubMed1993

Urinary excretion of bioactive amines and their metabolites in psychiatric patients receiving phenelzine.

Phenelzine [2-phenylethylhydrazine] (PLZ), a potent inhibitor of monoamine oxidase (MAO)-A and -B, is used widely in psychiatry. We have studied the effects of PLZ administration on urinary excretion of several bioactive amines and their metabolites in psychiatric patients. Urine samples (24-hour) were collected prior to treatment and again at 2 and 4 weeks of treatment with PLZ (30-90 mg daily in divided doses). Amines and metabolites analyzed included 2-phenylethylamine (PEA), m- and p-tyramine (m- and p-TA), phenylacetic acid (PAA), m- and p-hydroxyphenylacetic acid (m- and p-OH-PAA), tryptamine (T), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), normetanephrine (NME), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxytyramine (3-MT), and homovanillic acid (HVA). Levels of PEA, p-TA, 5-HT, and T were elevated during treatment with PLZ, but no significant changes in urinary excretion of the acid metabolites PAA, p-OH-PAA, and 5-HIAA were observed. Urinary levels of the noradrenaline metabolites NME and MHPG were increased and decreased, respectively; a similar pattern was observed with the dopamine metabolites 3-MT and HVA. There was an elevation in levels of m-TA and a decrease in its acid metabolite m-OH-PAA during the treatment with PLZ.

Adult↗
PubMed1988

Involvement of brain trace amines in the behavioural effects of phenelzine.

The MAO inhibitor phenelzine (PLZ) at a dose of 25 mg/kg does not affect the behavior of rats. In contrast, the equivalent dose of a deuterated analog (alpha, alpha, beta, beta-tetradeutero-PLZ, d4PLZ) elicits a biphasic behavioral syndrome in rats. In an attempt to correlate changes in cerebral monoamines with behavior, the concentration of various amines were measured at various times after the administration of either d4PLZ or PLZ (25 mg/kg). In general, PLZ and d4PLZ caused elevations in brain amine levels, particularly in the time period 2-12 hours after drug administration. Furthermore, d4PLZ increased the concentrations of serotonin (5-HT), phenylethylamine (PE), tryptamine (T), meta-tyramine (mTA), and 3-methoxytyramine (3-MT) to a greater extent than PLZ. Since the time course of behavioral excitation closely parallels the elevations in T and PE levels in the brain and since the percentage increases in PE and T levels following d4PLZ compared to PLZ treatment were substantially greater than those of the other amines, it was postulated that PE and T are involved in d4PLZ-induced behaviors.

Animals↗
PubMed1993

Analysis of biogenic amines in plasma of hypertensive patients and a control group.

Procedures were developed for the determination of 17 circulating amines using gas chromatography-negative ion chemical ionisation mass spectrometry. The amines were quantified against their appropriate deuterated isotopomers. The mean concentrations and ranges of catecholamines and trace amines were high compared with previous studies. In comparison with nonhypertensives, plasma from hypertensives had higher concentrations of the following amines: noradrenaline (t = 4.0%); normetanephrine (t = 6.1%) and metanephrine (t = 1.9%). There were no significant differences between 5HT levels in plasma from hypertensives and controls. The following trace amines could be detected in variable amounts in plasma: p-tyramine, m-tyramine, p-octopamine, m-octopamine, p-synephrine, m-synephrine, and salsolinol. The trace amines melatonin, N-acetyl 5HT, tryptamine, 6-hydroxymelatonin and 5-methoxytryptamine could not be detected in plasma with limits of detection lying in the range 20-100 pg ml-1.

Biogenic Amines↗
PubMed1993

NSD-1015 alters the gene expression of aromatic L-amino acid decarboxylase in rat PC12 pheochromocytoma cells.

Aromatic L-amino acid decarboxylase (AADC) is involved in the synthesis of the putative neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT), and trace amines some of which have been proposed as neuromodulators, such as 2-phenylethylamine and tryptamine. We report here that the gene expression of AADC can be regulated by the AADC inhibitor NSD-1015 in PC12 cells. The cells were treated with different doses of NSD-1015 (0.01-10 microM) for 3 days. Slot blot hybridization was performed to detect AADC mRNA and Western immunoblot to detect AADC protein. The cDNA probe for rat AADC was generated by reverse transcription from rat adrenal gland total RNA and was amplified by the polymerase chain reaction (PCR) method. The results demonstrated that NSD-1015 produced a concentration-dependent up-regulation in AADC mRNA levels which is followed by a stable increase in AADC protein. The results suggest that AADC is an enzyme that can be regulated at the level of gene expression. The finding may be of importance in the study of DA transmission and for an improved understanding of this enzyme.

Animals↗
PubMed1985

Quantitative aspects of the histochemical tetrazolium salt reaction on monoamine oxidase activity in rat liver.

The tetrazolium method for the histochemical detection of monoamine oxidase (MAO) activity in rat liver cryostat sections has been tested for its specificity and its possible use in quantification. The tetrazolium salt tetranitro blue tetrazolium is recommended for the localization of MAO activity, rather than nitro blue tetrazolium or BPST [2-(2-benzothiazolyl)-3-(4-phthalhydrazidyl)-5-styryl-tetrazolium] . Hardly any formazan was produced in the absence of the substrate tryptamine and Marsilid, a specific inhibitor of MAO activity, prevented formazan production almost completely. A linear relationship between the integrated absorbance measured with a microdensitometer and either the incubation period or section thickness was obtained. We conclude that the method described in this paper can be used for the quantitative analysis of MAO activity in tissue sections of rat liver. MAO activity was found to be 20-25% higher in the periportal zone of rat liver than in the perivenous zone.

Animals↗
PubMed1981

Inhibition of monoamine oxidase activity after combined action of chlordimeform with the antidepressant nialamide.

The 40-day oral administration of 5, 10, and 50 mg/kg chlordimeform to male rats moderately decreased monoamine oxidase activity (MAO) in the brain, liver, and serum, determined with the substrates kynuramine, tyramine, tryptamine, serotonin, dopamine, and benzylamine. The enzyme was inhibited predominantly in the liver. The study of MAO inhibition after 10 days application of 2, 6, 10, 15, and 20 mg/kg nialamide revealed that 2 mg/kg had a threshold effect. A dose of 6 mg/kg resulted in a pronounced decrease in the enzyme activity. Experiments with a 30-day application of 5, 10 and 50 mg/kg chlordimeform were made, followed by treatment with 6 mg/kg nialamide in combination for another 10 days. The statistical evaluation by the Student's t-test demonstrated increased MAO inhibitory action. Dose-effect relationship was established with kynuramine in liver, brain, and serum, and with benzylamine in liver.

Amidines↗
PubMed1995

[Automated pre-column derivatization with o-phthaldialdehyde (OPA)> A new RP-HPLC method for the determination of biogenic amines in food].

A simple, selective and highly sensitive HPLC method for the routine determination of the biogenic amines in food is presented. Sample preparation is based on a rapid amine extraction using 10% trichloroacetic acid and a cation exchange column for extract purification. For the RP-HPLC analysis OPA/2-mercaptoethanol is used for the pre-column derivatisation, followed by fluorescence detection (Ex 345 nm, Em 440 nm). The effects of several factors are discussed. A separation of 15 biogenic amines is achieved within 70 min. The recoveries for histamine, tyramine, putrescine, cadaverine, tryptamine and beta-phenylethylamine are higher than 95%. The detection limits lie between 0.1-0.5 pMol/injection (20 microliters), depending on the amine and a good linearity is achieved in the range from 0.5-500 pMol (r > 0.99). The method has been applied for the determination of biogenic amines in swiss cheese, salami, milk, beer and wine, the repeatability is very good.

Animals↗
PubMed1996

Biogenic amines in Spanish beers: differences among breweries.

Ten biogenic amines in Spanish beers were studied using HPLC, Agmatine, tyramine and putrescine were the prevailing amines, while histamine, beta-phenylethylamine, tryptamine, cadaverine, spermine and spermidine were detected at relatively low levels (in general < 2 mg/l). On the basis of the wide range of levels observed for tyramine (from 1.90 to 31.55 mg/l), the consumption of beer requires restriction in patients receiving monoamine oxidase inhibitor drugs. Biogenic amine levels in beers of the same type from the same company and from different companies were monitored every month over 1 year. Agmatine and putrescine levels showed minimal fluctuations in beers from the same company as well as from different breweries. Raw materials and brewing conditions would not affect the levels of those amines. However, tyramine levels were subject to wide fluctuations in beers produced by particular breweries irrespective of whether they were produced by the same company. Relatively high levels of tyramine were specific to some breweries.

Agmatine↗
PubMed1985

Characterization of 5-hydroxytryptamine binding sites in the plasma membrane of pig blood platelets.

Plasma membranes were isolated from pig platelets after glycerol facilitated lysis by sucrose density gradient centrifugation. The purity of the membrane fraction was followed by electron microscopy, gel electrophoresis and analysis of acid phosphatase (EC 3.1.3.2) and phosphodiesterases (EC 3.1.4.1). (3H)5-Hydroxytryptamine ([3H]5-HT) was bound to two saturable binding sites of the membranes. The KD value for the high affinity sites was 0.85 nM and for the low affinity sites 0.48 microM. With the exception of tryptamines little or no (3H)5-HT was displaced by serotonin antagonists and uptake inhibitors suggesting another type of binding than that of 5-HT1. Apparently, enhancement of binding in the presence of Na+ was due to stimulation of an uptake process. Binding of (3H)ketanserin and (3H)LSD to pig platelet membranes showed the characteristics of 5-HT2 binding sites previously identified in rat brain. Since ketanserin inhibited 5-HT induced aggregation of pig platelets (IC50 = 14.2 nM), the ketanserin binding sites can be classified as 5-HT2 receptors. The functional properties of these binding sites and their density in pig platelets as compared with brain membranes may motivate studies on 5-HT2 receptors in pig platelets as models for those in nerve endings.

Animals↗
PubMed1987

Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions.

Ipsapirone (TVX Q 7821, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxidehydrochloride), a new anxiolytic drug in respect of the evaluation of its effect on central 5-hydroxytryptamine (5-HT), noradrenaline and dopamine functions was studied. It was found that ipsapirone inhibits induced by 8-OH-DPAT and 5-methoxydimethyltryptamine (agonists of 5-HT1A receptors) behavioural effects (flat body posture and forepaw treading) in normal and reserpinized rats. Ipsapirone partly inhibited in rats but not in mice the 8-OH-DPAT-induced hypothermia. Ipsapirone, administered at high doses, decreased the body temperature in rats and mice, inhibited the 5-hydroxytryptophan-induced head twitches in mice and the tryptamine-induced convulsions and tremor in rats. In the hind limb flexor reflex preparation of the spinal rat only high doses of the drug inhibited stimulation induced by quipazine, m-chlorphenylpiperazine, 8-OH-DPAT and St 587 (an agonist of alpha 1-adrenoceptors). Ipsapirone did not block the fenfluramine- and m-chlorphenylpiperazine-induced hyperthermia in rats at an ambient temperature of 28 degrees C. The drug did not affect clonidine-induced sedation and inconsiderably attenuated clonidine-induced hypothermia in mice. It attenuated the d-amphetamine-induced locomotor hyperactivity in mice and rats but, given alone, decreased the locomotor activity. The obtained results indicate that ipsapirone exhibits 5-HT1A antagonistic effect, and only at high doses it can also produce an inhibitory effect on 5-HT2 and the alpha 1-adrenergic function.

Animals↗
PubMed1985

The effect of reduced neopterin on the synthesis of several methylated indoles in the pineal gland of adult male golden hamsters, kept under standardized conditions.

In the present study the effect was tested of reduced neopterin (RN) on the methylating capacity of the pineal gland of adult, male golden hamsters, housed under standardized conditions throughout the year. An effect of RN on the synthesis of a number of methylated compounds was, indeed, demonstrated. It is concluded that RN not only influences the indole metabolism by being the cofactor of tryptophan-hydroxylase, but that it might be involved in the regulation of other enzymes as well. Incubation with RN was most effective at the end of the light period. As this is also the time at which melatonin (aMT) injections cause gonadal atrophy in hamsters, kept under long photoperiod, this time of the day may be very important for aMT synthesis. A season-bound influence of RN was also demonstrated. The effect of RN was stimulatory in September, November and January for 5-methoxy-tryptamine (MT) and in November for 5-methoxytryptophan (MW) synthesis, but inhibitory in July. Furthermore, the effect of RN was stimulating for 5-methoxyindole-3-acetic acid (MA) and aMT in September, while the influence in the other months tested was absent or slightly inhibiting. These results suggest that the influence of RN in the pineal may be regulatory to various enzymes of the indole metabolism.

5-Hydroxytryptophan↗
PubMed1991

Lithium-selective permeation through lipid bilayer membranes mediated by a di-imide ionophore with nonsymmetrical imide substituents (ETH1810).

The neutral, noncyclic Li(+)-selective ionophore ETH1810, which is a di-imide, differs structurally from previous similar ionophores by removal of the intramolecular symmetry of the N-imide substituents. Properties of this ionophore, as a potential carrier of lithium, were probed through studies of ionophore-induced changes in electrical properties of lipid bilayer membranes. ETH1810 was found capable of transporting lithium and other monovalent cations, across lipid bilayer membranes, forming 2:1 ionophore:ion membrane-permeating species. It was found to be 10-fold more potent than ETH1644, which was the previous best ionophore of this type. The selectivity sequence among alkali cations was found to be: Li+ (1) greater than Na+ (0.009) greater than K+ (0.004) greater than Cs+ (0.0035). Among the physiological alkali cations, it constitutes a 40 (vs. Na+) to 160% (vs. K+) improvement over ETH1644. ETH1810 was also found to be capable of acting as a carrier of biogenic amines and related molecules, with the following selectivity sequence:tryptamine (20) greater than phenylethylamine (7.8) greater than tyramine (4.3) greater than serotonin (2.5) greater than Li+ (1) greater than NH+4 (0.013) greater than dopamine (0.012). It was found that protons, at physiological concentrations, do not interfere with the lithium transport mediated by ETH1810. The relationship between the improvements in ionic selectivity and potency vs. the differences in structural features is discussed.

Biogenic Amines↗
PubMed1985

Selective transport of Li+ across lipid bilayer membranes mediated by an ionophore of novel design (ETH1644).

The neutral noncyclic, lithium-selective ionophore ETH1644, which is structurally different from previously available ionophores of this type, is a selective carrier of Li+ in lipid bilayer membranes of various lipid composition. The ionophore forms a 2:1 carrier/cation complex, and the rate-limiting step in the overall transport process is the diffusion of the carrier/ion complex across the membrane. The selectivity sequence for lithium vs. other ions normally found in biological systems is: Li+ (1) greater than Na+ (0.017) greater than or equal to K+ (0.017) greater than Cl- (0.001), Ca2+ and Mg2+ are impermeant. At neutral pH protons do not interfere with the Li+-carrying ability of this ionophore. On the basis of structural differences and supported by conductance data, it is argued that the improved selectivity of Li+ over the other alkali cations is due more to a decrease in the affinities of the ionophore for the latter cations that to an increase of its affinity to Li+. This ionophore can also act as a carrier of biogenic amines (catecholes, indoles and derivatives), with the structure of the permeant species and mechanism of permeation similar to that observed with the alkali cations. The selectivity sequence is: tryptamine (18.1) greater than phenylethylamine (11.6) greater than tyramine (2.4) greater than Li+ (1) greater than serotonin (0.34) greater than epinephrine (0.09) greater than dopamine (0.05) greater than norepinephrine (0.02), showing the ionophore to be more selective to Li+ than to any of the neurotransmitters studied.

Amides↗
PubMed1993

Presence in and effects of pineal indoleamines at very low level of phylogeny.

The unicellular organism Tetrahymena contains serotonin and is able to take up the hormone from its milieu. The serotonin content of the cell changes as a function of the presence of foreign exogenous hormones. This indicates a possible role of serotonin as a chemical mediator. Exogenous serotonin stimulates the RNA synthesis of Tetrahymena, and it was the only one among the hormones studied which kept the RNA level durably high. Serotonin stimulates phagocytosis and growth of Tetrahymena, and its precursors also stimulate growth. Serotonin can imprint Tetrahymena, and as a consequence of this the effect of the hormone increases in the case of further encounters. Treatment with serotonin-related molecules soon after imprinting can reduce the effect of imprinting. Melatonin can contract the pigment cells of Planaria; however, its precursors serotonin and tryptamine can do this more intensely. Both melatonin and serotonin can influence the regeneration of Planaria, with effects which differ when different phenomena are studied. Evolutionary theories are discussed.

Animals↗
PubMed1987

Coexistence of peptides with classical neurotransmitters.

In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed.

Animals↗